2,3-dihydro-4H-1,3-benzoxazin-4-one derivatives as modulators of cholinergic muscarinic M1 receptor
The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof: wherein each symbol is as defined in the attached DESCRIPTION.
1. A compound represented by the formula
wherein
R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group;
R 3 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group,
(3) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups,
(4) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms or
(5) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(iv) a C 2-6 alkenyl group,
(v) a C 2-6 alkynyl group optionally substituted by a tri-C 1-6 alkylsilyl group,
(vi) a C 1-6 alkoxy group,
(vii) a C 1-6 alkoxy-carbonyl group and
(Viii) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 1-6 alkyl group,
or a salt thereof.
2. The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group
R 3 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group,
(3) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups,
(4) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms or
(5) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a 6-membered aromatic ring optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group,
(iv) a C 2-6 alkenyl group,
(v) a C 2-6 alkynyl group optionally substituted by a tri-C 1-6 alkylsilyl group,
(vi) a C 1-6 alkoxy group and
(vii) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 1-6 alkyl group,
or a salt thereof.
3. The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group;
R 3 is
(1) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups or
(2) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group,
(iv) a C 1-6 alkoxy group and
(v) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6 alkyl groups,
or a salt thereof.
4. The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group:
R 2 is a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group;
R 3 is
(1) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups or
(2) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group,
(iv) a C 1 - 6 alkoxy group and
(v) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6 alkyl groups,
or a salt thereof.
5. The compound according to claim 1 , wherein R 1 is a hydrogen atom or a halogen atom:
R 2 is a C 1-6 alkyl group;
R 3 is
(1) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups or
(2) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom,
(ii) a C 1-6 alkyl group and
(iii) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6 alkyl groups,
or a salt thereof.
6. A pharmaceutical composition comprising the compound according to claim 1 or a salt thereof, and a pharmaceutically acceptable carrier.